| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
GP262 (0-5 μM, 0-24 hours) can effectively reduce the levels of PI3K and mTOR in MDA-MB-231 cells. This degradation can be weakened by 26S proteasome inhibition, blocked by high concentrations of competitive agents (MG132 and VH032), and depends on the recruitment of VHL[1]. GP262 (8-1000 nM) can significantly inhibit cell proliferation and induce programmed cell death (apoptosis). It showed dose-dependent growth inhibition in MDA-MB-231, MCF-7 and MDA-MB-361 cells, with IC50 values of 68.0 nM, 161.6 nM and 124.2 nM, respectively, and maximum inhibition rates (Imax) of 65.4%, 83.4% and 97.7%, respectively. At a concentration of 200 nM, it can inhibit the clonogenic ability of MDA-MB-231 cells. In MCF-7 cells, it has inhibitory ability on mTOR and PI3Kα with IC50 values of 167.6 and 40.0 nM, respectively [1]. GP262 (8-5000 nM, 24 h) showed a concentration-dependent decrease in PI3Kγ protein levels in THP-1 cells and exhibited an antiproliferative effect in OCI-AML3 (IC50 = 44.3 nM) and THP-1 cells (IC50 = 48.3 nM) [1]. GP262 (1000 nM, 12 h) increased the apoptosis rate of MDA-MB-231 cells to 32.1% [1]. The dissociation constants (Kd) of GP262 (0.03125-2 μM) with PI3Kα and mTOR were 0.867 μM and 0.479 μM, respectively [1]. GP262 can induce a polyubiquitination-dependent proteasome degradation pathway [1]. GP262 exhibits excellent selectivity for PI3K family and mTOR kinases, thereby triggering extensive transcriptomic alterations in MDA-MB-231 cells, including multiple differentially expressed genes related to cell cycle regulation, cancer-related processes and apoptosis. These alterations collectively indicate that it has a significant enrichment effect and profound impact on cell cycle-related pathways [1].
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|---|---|
| ln Vivo |
GP262 (15 or 25 mg/kg, intraperitoneal injection, once daily for 20 days) effectively reduced the levels of target proteins (PI3K and mTOR) in the NOD-SCI model of triple-negative breast cancer xenograft in MDA-MB-231, significantly inhibited tumor growth, and showed excellent safety and tolerability without causing significant systemic toxicity or organ damage [1].
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: MDA-MB-231 cells Tested Concentrations: 8, 40, 200, 1000 and 5000 nM Incubation Duration: 0, 3, 6, 9, 12 and 24 h Experimental Results: Induced degradation of p110α with a DC50 of 227.4 nM and a Dmax of 71.3%. Induced degradation of p110γ with a DC50 of 42.23 nM and a Dmax of 88.6%. Induced degradation of mTOR with a DC50 of 45.4 nM and a Dmax of 74.9%. Significantly inhibited AKT activation (p-AKT) without affecting the total AKT protein levels. Reduced p85, p-GSK and p-4EBP1 protein level. Induced time-dependent proteolysis of mTOR and p110α at 1 μM, exhibiting significant degradation within 12 h and maximal efficiency by 24 h, and this effect was markedly attenuated upon 26S proteasome inhibition and was also inhibited by siRNA-mediated VHL knockdown (500 nM, 24 h). Western Blot Analysis[1] Cell Types: THP-1 cells Tested Concentrations: 8, 40, 200, 1000 and 5000 nM Incubation Duration: 24 h Experimental Results: Demonstrated concentration-dependent reduction of PI3Kγ protein levels (DC50 = 88.4 nM) with >70% maximal degradation efficiency achieved after 24-h treatment. |
| Animal Protocol |
Animal/Disease Models: MDA MB-231 cells induced-female NOD-SCID mice (60-70 days old, 22-24 g)[1]
Doses: 15 or 25 mg/kg Route of Administration: i.p., daily for 20 consecutive days Experimental Results: Showed 57.8% tumor growth inhibition at 15 mg/kg and 79.2% tumor growth inhibition at 25 mg/kg. Maintained body weight fluctuations within 10%. Reduced PI3K and mTOR protein expression. Decreased expression of the proliferation marker KI67. Showed no significantly inflammatory infiltration, necrosis, or structural abnormalities in major organs (heart, liver, and kidney). |
| References |
| Molecular Formula |
C56H72N12O8S
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|---|---|
| Molecular Weight |
1073.31
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| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9317 mL | 4.6585 mL | 9.3170 mL | |
| 5 mM | 0.1863 mL | 0.9317 mL | 1.8634 mL | |
| 10 mM | 0.0932 mL | 0.4658 mL | 0.9317 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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